Faculty | Xiangyu LIU, Ph.D.

Xiangyu LIU

Assistant Professor, Principal Investigator

Dr. Xiangyu Liu obtained his BS and PhD at Peking University in 2004 and 2011, respectively. From 2008 to 2010, he studied as an exchange PhD student at Aarhus University, Denmark, with the support from Chinese Scholarship Council. Dr. Liu conducted his first postdoctoral research at School of Life Sciences, Peking University from 2011 to 2013, and his second postdoctoral research at School of Medicine, Tsinghua University from 2013 to 2017. Then he worked as assistant researcher at School of Medicine, Tsinghua University. In August 2019, Dr. Liu joined School of Pharmaceutical Sciences as an assistant professor and a principle investigator, his research interest focuses on structural biology of G protein coupled receptors and structure guided drug development.

 

Research Interests

G protein coupled receptors (GPCRs) are a group of membrane receptors with seven transmembrane helices. They sense various signals from outside of the cells, transfer the signals to intracellular pathways and modulate cellular responses to environment. The ligands of GPCRs include odorants, hormones, neurotransmitters, chemokines, et al. GPCRs are targets of approximately 30% commercially available medicines. Structural studies on GPCRs have made great progress in the past decade, however the structural basis of receptor-G protein selectivity and the molecular mechanism of biased signaling remain unclear. My lab aims to elucidate structures of disease related GPCRs and structure-based drug development. We also aim to develop novel methods to find GPCR drugs.

Scientific Contributions 

Elucidated the molecular mechanisms of how allosteric modulators regulate the function of the β2 adrenergic receptor (β2AR). Provided guidace to the development of allosteric drugs for GPCRs.
Proposed the model of the dynamic process of GPCR-G protein complex formation.

 Selected Achievements

1.Identified the binding pockets of the first intracellular allosteric agonist and the first intracellular allosteric antagonist of the β2 adrenergic receptor, elucidated the molecular mechanism of how the allosteric modulators regulate receptor function. (Science, 2019. Nature, 2017)
2.Uncovered a potential intermediate state of GPCR-G protein complex formation. Developed a novel method to stabilize the active conformation of GPCR by fusing with the carboxyl terminal peptide of G protein. (Cell, 2019)
3.Developed M3 muscarinic receptor selective ligands based on a single amino acid difference between the orthosteric ligand binding pockets of the M2 muscarinic receptor and M3 muscarinic receptor. (PNAS, 2018)
4.Solved the high-resolution crystal structure of the first heavy metal transporting P-type ATPase (copper pump) and elucidated the copper transporting mechanism. (Nature, 2011)

Honors and Awards

2013-2017 Amgen-China Postdoc Scholarship
2012-2013 Postdoc foundation from the Peking-Tsinghua Center for Life Sciences.

Selected Publications

1. Xiangyu Liu*, Ali Masoudi*, Alem W. Kahsai*, Li-Yin Huang, Biswaranjan Pani, Dean P. Staus, Paul J. Shim, Kunio Hirata, Rishabh K. Simhal, Allison M. Schwalb, Paula K. Rambarat, Seungkirl Ahn, Robert J. Lefkowitz#, Brian Kobilka#. Mechanism of β2AR regulation by an intracellular positive allosteric modulator. Science (2019) 364 (6447), 1283-1287.
2.Xiangyu Liu*#, Xinyu Xu*, Daniel Hilger*, Philipp Aschauer, Johanna K.S. Tiemann, Yang Du, Hongtao Liu, Kunio Hirata, Xiaoou Sun, Ramon Guixà-González, Jesper M. Mathiesen, Peter W. Hildebrand, Brian K. Kobilka#. Structural insights into the process of GPCR-G protein complex formation, Cell (2019) 177(5), 1243-1251.
3. Hongtao Liu*, Josefa Hofmann*, Inbar Fish*, Benjamin Schaake, Katrin Eitel, Amelie Bartuschat, Jonas Kaindl, Hannelore Rampp, Ashutosh Banerjee, Harald Hübner, Mary J. Clark, Sandra G. Vincent , John T. Fisher, Markus R. Heinrich, Kunio Hirata, Xiangyu Liu#, Roger K. Sunahara, Brian K. Shoichet#, Brian K. Kobilka#, Peter Gmeiner#. Structure-guided development of selective muscarinic M3 acetylcholine receptor antagonists. PNAS (2018) 115(47):12046-12050.
4. Xiangyu Liu*, Seungkirl Ahn*, Alem W. Kahsai, Kai-Cheng Meng, Naomi R. Latorraca, Biswaranjan Pani, A. J. Venkatakrishnan, Ali Masoudi, William I. Weis, Ron O. Dror, Xin Chen, Robert J. Lefkowitz# & Brian K. Kobilka#. Mechanism of intracellular allosteric β2AR antagonist revealed by X-ray crystal structure, Nature (2017) 548, 480-484.
5. Yi-He Huang*, Xiang-Yu Liu*, Xiao-Xia Du, Zheng-Fan Jiang & Xiao-Dong Su#. The Structural Basis for the Sensing and Binding of Cyclic di-GMP by STING, Nature Structural & Molecular Biology (2012) 19, 728–730.
6. Pontus Gourdon*, Xiang-Yu Liu*, Tina Skjørringe, J. Preben Morth, Lisbeth Birk Møller#, Bjørn Panyella Pedersen & Poul Nissen#. Crystal structure of a copper-transporting PIB-type ATPase, Nature (2011) 475, 59-64.
7. Luo Feng*, Gui Xinrui*, Zhou Heng*, Gu Jinge, Li Yichen, Liu Xiangyu, Zhao Minglei, Li Dan#, Li Xueming#, Liu Cong#. Atomic structures of FUS LC domain segments reveal bases for reversible amyloid fibril formation, Nature Structural & Molecular Biology (2018) 25 (4), 341–346.
8. Pikyee Ma, Dietmar Weichert, Luba A Aleksandrov, Timothy J Jensen, John R Riordan, Xiangyu Liu, Brian K Kobilka & Martin Caffrey. The cubicon method for concentrating membrane proteins in the cubic mesophase, Nature Protocols (2017) 12, 1745–1762.
9. Chia-Ying Huang, Vincent Olieric, Pikyee Ma, Nicole Howe, Lutz Vogeley, Xiangyu Liu, Rangana Warshamanage, Tobias Weinert, Ezequiel Panepucci, Brian Kobilka, Kay Diederichs, Meitian Wang and Martin Caffrey. In meso in situ serial X-ray crystallography of soluble and membrane proteins at cryogenic temperatures, Acta Crystallogr D Struct Biol. (2016) 72: 93–112.
10. Bjørn Panyella Pedersen, Pontus Gourdon, Xiangyu Liu, Jesper Lykkegaard Karlsen and Poul Nissen. Initiating heavy-atom-based phasing by multi-dimensional molecular replacement. Acta Crystallogr D Struct Biol. (2016) 72: 440–445.
11. Pontus Gourdon, Jacob Lauwring Andersen, Kim L. Hein, Maike Bublitz, Bjørn P.Pedersen, Xiang-Yu Liu, Laure Yatime, Maria Nyblom, Thorbjørn Terndrup Nielsen, Claus Olesen, Jesper V. Møller, Poul Nissen & J. Preben Morth. HiLiDe - A systematic approach to membrane protein crystallization in high lipid and detergent concentrations. Crystal Growth & Design (2011) 11 (6), 2098–2106.